Cardio Exam 3: Fooshy (HF)

Heart Failure

• A clinical syndrome caused by inability of the heart to supply blood to meet ______

• A clinical syndrome with ______ and corroborated by ______ levels and/or ______ evidence of ______

• ______ is a subset of HF characterized by ______ and ______

tissue metabolic requirements, S/Sxs caused by structural and/or functional cardiac abnormality, elevated natriuretic peptide (NP), objective, pulmonary or systemic congestion, CHF, LV systolic dysfunction (LVSD), volume excess

Heart Failure

• RV pumps ______ blood to the ______ via ______

• LV pumps ______ blood to the ______ via ______

• RV → ______ circulation

• LV → ______ circulation

deoxygenated, lungs, pulmonary arteries, oxygenated, systemic circulation, aorta, pulmonary, systemic

Flow

• Q = Change in P / R

• R = Resistance

• Q = Flow

• ______ is the driving force for flow

• R is the ______

Change in P, force that impedes flow

Pressure 

• Upstream pressure for the CV system → ______

• The ______ pressure for the CV system in the ______

Aorta, downstream, right atrium (RA)

Resistance

• ______ is the dominant variable that determines the resistance

• ______ is opposite/inverse of Resistance

Radius, radius

Ejection Fraction

• Ventricular performance → fraction of ______ ejected from the ______ during ______

  • EF = SV / EDV

  • ______ = ______ → determined by ______

end-diastolic volume, ventricles, systole, SV, Stroke Volume, preload, afterload, and contractility

Frank-Starling Principle

• ______ produces a ______ stretch of heart muscle → ______

• ______ → amt of blood ejected from the ventricle with each cardiac cycle

• ______ → amt of blood in heart’s LV just before the heart contracts

Increased diastolic filling, greater, larger SV, Stroke Volume, End-Diastolic Volume

Key Mediators of CO

• ______ → ______ SV

• ______ → ______ SV

• ______ → ______ CO

Increased Contractility and Preload, Increased, Increased Afterload, Decreased, Increased SV and HR, Increased

Preload

• Ventricles are ______

stretched prior to contracting

Afterload

• ______ → ______

Aortic pressure during systole, increased resistance

Contractility (Inotropic state)

• Changes in ______ for a given set of ______ conditions → ______ influences

myocardial force, preload and afterload, chemical and hormonal

Cardiac Function → ______

Right Arterial Pressure

What does this image show?

Aortic Pressure

What does this image show?

Peripheral Circulation

CV ______

• Resting ______

• Cardiac ______

Integration, CO and BP, function

Conditions that Cause Left-Sided HF

KNOW IMAGE

Conditions that Cause LEFT-Sided HF IMAGE

• Impaired Contractility → ______

  • ______: ______ Myocardial Ischemia

  • ______: ______

  • ______ Cardiomyopathies

• Increased Afterload (______ pressure overload) → ______

  • ______ Stenosis

  • ______

• REF → ______ → Preserved ______ (______) → Impaired ______

  • ______

  • ______ Cardiomyopathy

  • Myocardial ______

  • ______ Myocardial Ischemia

  • Pericardial ______ or ______

Reduced EF, CAD, MI and Transient, Chronic Volume Overload, Mitral and Aortic Regurgitation, Dilated, chronic, Reduced RF, Advanced Aortic, Uncontrolled Severe HTN, HF, EF, Diastolic Dysfunction, diastolic filling, LV Hypertrophy, Restrictive, Fibrosis, Transient, Constriction, Tamponade

Compensatory Mechanisms In HF

KNOW IMAGE

What is B?

HF

What is C?

HF (compensated)

______

• Kidney: ______ → ______

• Kidney: ______

HF (Decompensated), Aldosterone, decreased Na excretion, Volume Retention

Heart Failure (Decompensated) Overall Sxs:

• ______

• ______ (______): Due to ______

• ______ (______): Due to ______

• Reduced ______: Due to ______

• ______ hypertrophy

Na retention, Edema, fluid retention, Na retention, Dyspnea, SoB, pulmonary edema, exercise capacity, dyspnea, Ventricular

______ → ______

Diuretics in HP, decreased blood volume

______ → ______

Vasodilators in HF, decreased BP

______ → ______

Inotropic Agents in HF, Increased CO

______ → ______

Nitrates in HF, Venous Smooth muscle relaxation

Ion Movements during Contraction of Cardiac Muscle

• Drugs ______ → ______ (sustained)

• ______ (SR) → ______ entry from ______ triggers the release of ______ → ______ concentration → initiates the ______ → ______ by ______ and by extrusion from cell by ______ → ______ is restored by ______ (______ Na out and ______ K in)

increasing intracellular Ca levels, increases contraction force, Ca stores, Ca, outside the cell, lots of Ca from SR, increased Ca, contractile process, Ca removed, reuptake into the SR, Ca/Na exchange, no balance, Na/K ATPase, 2, 1

Compensatory Physiologic Responses in HF

KNOW IMAGE

Compensatory Physiologic Responses in HF IMAGE

• Decreased CO Leads to…

  • ______ (______)

    • ______ contractility, HR, and vasoconstriction

      • + → ______

      • – → ______ (______ → lead to ______)

  • ______

    • Decreased ______ → ______ → increased ______ → increased ______ levels

      • + → effective circulating ______/______

      • – → ______, leading to increased ______

  • ______

    • Increased ______

      • + → ______

      • – → ______

SNS Activation, releases catecholamines, increased, increases preload, SV, and CO, Afterload, increase oxygen demand, HF, RAAS Activation, renal perfusion, renin release, Ang II, aldosterone, volume, increased preload, increased vasoconstriction, afterload, Increased ADH, circulating volume, increased preload, pulmonary edema

Compensatory Physiologic Responses in HF IMAGE

• More specifically/info Part 1

  • ______ sympathetic activity → ______ → Enhanced ______ and increased ______ → increased ______ → increased ______

  • Activation of RAAS System → ______ and ______ (______)

  • Compensatory responses ______ the workload of the heart as well, contributing to a ______

Increased, vasoconstriction, venous return, cardiac preload, stroke volume, CO, increased peripheral resistance/afterload, Na and water retention, preload, increase, continuous decline in cardiac function

Compensatory Physiologic Responses in HF IMAGE

• More specifically/info Part 2

  • ______ of Natriuretic Peptides → ______ of Natriuretic peptides → beneficial response may improve ______ and ______

  • Myocardial Hypertropy → Frank-Starling mechanism ______ in direct response to ______

  • ______ and ______

  • ______ to Natriuretic Peptides → ______ → ______

Activation, increased preload and release, cardiac function, HF Sxs, increased SV, increased preload, Increased inflammation, oxidative stress, Resistance, increased preload, Pressure overload

ACE-Is

• Decreased vascular resistance (afterload) and venous tone (preload) → increased CO

• Decreased production of Ang II and aldosterone → decreased retention of Na and water

ACE-Is

ACE-Is

• ______ and ______ → ______

• Decreased production of ______ → decreased ______

• Ex.

  • ______

  • ______

  • ______

  • ______

  • ______

  • ______

Decreased vascular resistance (afterload), venous tone (preload), increased CO, Ang II and aldosterone, Na and water retention, Captopril, Enalapril (Vasotec), Fosinopril, Lisinopril (Qbrelis, Zestril), Quinapril (Accupril), Ramipril (Altace)

______

• Decreased afterload and preload in HF pts

• Use if pt cannot tolerate ACE-Is due to cough or angioedema

• C/I in pregnancy

ARBs

ARBs

• ______

• Use if pt ______ due to ______

• ______

• Ex.

  • ______

  • ______

  • ______

  • ______

Decreased preload and afterload in HF pts, cannot tolerate ACE-Is, cough or angioedema, C/I in pregnancy, Candesartan (Atacand), Losartan (Cozaar), Telmisartan (Micardis), Valsartan (Diovan)

______

• Antagonists of aldosterone at the mineralocorticoid receptor

• Prevent Na retention, myocardial hypertrophy, and hypokalemia

MRAs

MRAs

• Antagonists of ______ at the ______

• Prevent ______, myocardial ______, and ______

• Spironolactone → binds to ______ receptors.

• Eplerenone → ______ receptors → fewer ______ (ex. gynecomastia) than spironolactone. 

• Ex.

  • ______

  • ______

aldosterone, MR, Na retention, hypertrophy, hypokalemia, progesterone and androgen, more selective for aldosterone, endocrine effects, Eplerenone (Inspra), Spironolactone (Aldactone)

Angiotensin Receptor–Neprilysin Inhibitors (ARNI)

• Inhibition of neprilysin→  increased vasoactive peptides activity

• ARB → combined with a neprilysin inhibitor (sacubitril).

Angiotensin Receptor-Neprilysin Inhibitors (ARNI)

Angiotensin Receptor–Neprilysin Inhibitors (ARNI)

• Inhibition of neprilysin→  ______ activity

• ______ → combined with a neprilysin inhibitor (______).

• ______ = ARNI.

• Sacubitril/valsartan → ______

• Ex.

  • ______

• Inhibition of neprilysin → ______ → ______

increased vasoactive peptide, ARB, Sacubitril, Sacubitril/Valsartan, decreased afterload, preload, and myocardial fibrosis, Sacubitril/Valsartan (Entresto), increased bradykinin levels, increased angioedema

BBs

• ______ activity

• Improved ______ and ______ cardiac remodeling despite the initial exacerbation of Sxs → ______ → ______ → prevents deleterious effects of ______ on the cardiac ______ → ______, ______, and ______

• ______ → nonselective beta-adrenergic receptor antagonist and blocks alpha-adrenergic receptors

• ______ → beta-1 selective antagonists and metabolized by CYP2D6

• ______ → P-gp substrate

• Ex.

  • ______

  • ______

  • ______

  • ______

negative inotropic, systolic function, reverse, decreased HR, inhibits renin release from the kidneys, NE, muscle fibers, Decreased remodeling, hypertrophy, cell death, Carvedilol, Bisoprolol and Metoprolol Succinate, Carvedilol, Bisoprolol, Carvedilol (Coreg, Coreg CR), Metoprolol Succinate (Toprol XL), Metoprolol Tartrate (Lopressor)

______

• Negative inotropic activity

• Improved systolic function and reverse cardiac remodeling despite the initial exacerbation of Sxs → decreasing HR → inhibits the renin release from kidneys → prevents deleterious effects of NE on the cardiac muscle fibers → decreased remodeling, hypertrophy, and cell death

BBs

______

• Decreased preload  → decreased venous return

• Decreased plasma volume → decreased afterload

• ______ → most used ______ in HF pts

• Decreased S/Sxs of volume overload (e.g., dyspnea, peripheral edema)

Diuretics, Loop Diuretics, diuretic

Diuretics

• ______  → ______

• ______ → ______

• Loop diuretics → ______

• ______ of ______ (e.g., dyspnea, peripheral edema)

• Ex. 

  • ______

  • ______

  • ______

  • ______

Decreased preload, decreased venous return, decreased plasma volume, decreased afterload, most used diuretics in HF pts, Decreased S/Sx, volume overload, Bumetanide (Bumex), Furosemide (Lasix), Metolazone (Zaroxolyn), Torsemide (Soaanz)

______

• Pacemaker Action Potential

• Slowed diastolic depolarization in the SA node → decreased HR 

• Effect is dose dependent

• Ex.

  • Ivabradine (Corlanor)

• Block similar channels in the eye

• C/I in pregnancy, breast feeding, advanced heart block, or with potent 3A4 inhibitors

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blockers (HCN Channel Blockers)

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blockers (HCN Channel Blockers)

• ______ action potential

• ______ in the ______ node → ______ 

• Effect is ______

• Ex.

  • ______

• Block similar channels in the ______

• C/I in ______, ______, ______, or ______

pacemaker, slowed diastolic depolarization, SA, decreased HR, dose-dependent, Ivabradine (Corlanor), eye, pregnancy, breastfeeding, advanced heart block, potent 3A4 inhibitors

______

• Decreased Ca in arteriole smooth muscle → Decreased afterload

• Inhibits oxidases → increased NO levels and vasodilation → Decreased preload and afterload

• It is often used with an oral nitrate (isosorbide dinitrate) in HF

Arterial Vasodilators

Arterial Vasodilators

• ______ in arteriole ______ → ______

• Inhibits ______ → ______ levels and ______ → ______

• It is often used with an ______ (______) in HF

• Ex. 

  • ______

  • ______

  • FDC ______

  • ______

  • ______

Decreased Ca, smooth muscle, decreased afterload, oxidases, increased NO, vasodilation, Decreased preload and afterload, oral nitrate, isosorbide dinitrate, Hydralazine, Isosorbide Dinitrate (Dilatrate-SR, Isordil), Hydralazine/Isosorbide Dinitrate (Bidil), Nitroglycerin, Nitroprusside (Nipride, Nitropress)

______

• Nitrates → more venodilation than arterial dilation

• Nitroprusside → more balanced

Arterial and Venous Vasodilators

Arterial and Venous Vasodilators

• ______ → more ______ than ______

• ______ → more ______

Nitrates, venodilation, arterial dilation, Nitroprusside, balanced

______

• Decreased preload and afterload

• Decreased glucose and Na reabsorption by inhibiting SGLT2 in the proximal tubule

• Cardioprotective effect → inhibition of the Na/H exchanger → prevents Ca overload and contributes to natriuresis

• Ex.

  • Dapagliflozin (Farxiga)

  • Empagliflozin (Jardiance)

Na-Glucose Cotransporter 2 Inhibitors (SGLTIs)

Sodium–Glucose Cotransporter 2 Inhibitors (SGLTIs)

• ______

• ______ reabsorption by inhibiting SGLT2 in the ______

• ______ effect → inhibition of the ______ → prevents ______ and contributes to ______

• Ex.

  • ______

  • ______

Decreased preload and afterload, decreased glucose and Na, proximal tubule, Cardioprotective, Na/H exchanger, Ca overload, natriuresis, Dapagliflozin (Farxiga), Empagliflozin (Jardiance)

______

• Directly stimulates sGC through a different binding site than NO and sensitizes sGC to endogenous NO

• Ex.

  • Vericiguat (Verquvo)

Soluble Guanylate Cyclase Stimulators

Soluble Guanylate Cyclase Stimulators

• Directly stimulates ______ through a different binding site than ______ and sensitizes ______ to endogenous ______

• Ex.

  • ______

sGC, NO, sGC, NO, Vericiguat (Verquvo)

Inotropic Drugs

• ______

• Ex. 

  • ______

  • ______

  • ______

  • ______

increased contractility and CO, Digoxin (Lanoxin), Dobutamine (Dobutrex), DA, Milrinone

Explain this image related to inotropic drugs.

• A → ______

• A to B → ______

• B to C → ______ → ______

• C to D → ______ → ______

normal healthy heart, initial reduction in contractility in HF, increased Ventricular end-diastolic pressure, adequate CO, increased contractility, increased CO

______

• Increased contractility of heart muscle

• Only available digitalis glycoside is digoxin

• Inhibition of Na/K-adenosine triphosphatase (ATPase) enzyme → decreased myocyte activity to pump Na from the cell → increased free Ca → increased cardiac contractility

• Increased vagal tone → Decreased HR and myocardial oxygen demand 

• Slows conduction velocity through the AV node (useful for AFib).

• Lower doses → digoxin more likely to inhibit neurohormonal activation w/o positive inotropic effects

• Low serum drug concentration→ beneficial in HFrEF

Inotropic Drugs - Digitalis Glycosides

Inotropic Drugs – Digitalis Glycosides

• ______ of heart muscle

• Only available digitalis glycoside is ______

• Inhibition of ______ → ______ activity to pump ______ from the cell → ______ → ______

• ______ → ______ and myocardial ______ 

• ______ velocity through the ______ node (useful for ______).

• Lower doses → digoxin more likely to inhibit ______ w/o ______ effects

• Low serum drug concentration→ beneficial in ______

Increased contractility, digoxin, Na/K ATPase, decreased myocyte, Na, increased free Ca, increased contractility, Increased vagal tone, decreased HR, oxygen demand, slows conduction, AV, Afib, neurohormonal activation, positive inotropic, HFrEF

______

• Large Vd and Well tolerated at lower doses

• Eliminated intact by the kidney → require dose adjustment in renal dysfunction

• IncreaseD the risk of arrhythmias

• Digoxin is a substrate of P-gp → P-gp Inhibitors (increase digoxin levels)

Inotropic Drugs - Digoxin

Inotropic Drugs - Digoxin

• ______ and Well tolerated at ______ doses

• Eliminated intact by the ______ → require ______ in ______

• ______ the risk of ______

• Digoxin is a substrate of ______ → P-gp Inhibitors (______ digoxin levels)

Large Vd, lower, kidney, dose adjustment, renal dysfunction, increased, arrhythmias, P-gp subsrate, increased

______

• Dobutamine and DA → positive inotropic effects and vasodilation (in the case of dobutamine) → improve cardiac performance

• Increased Ca entry into myocardial cells and contraction

• IV infusion

• Short-term treatment of acute decompensated HF in the hospital

• Binding of a Beta-adrenergic agonist, such as DA or Dobutamine → activates AC → produces cAMP → cAMP activates protein kinase → phosphorylates Ca channels → increased Ca flow into the cell → Increased contraction force of heart muscle

Inotropic Drugs - Beta-Adrenergic Agonists

Inotropic Drugs - Beta-Adrenergic Agonists

• ______ → ______ effects and ______ (in the case of ______) → improve cardiac performance

• ______ entry into ______ cells and ______

• ______

• ______-term treatment of acute ______ in the hospital

• Binding of a Beta-adrenergic agonist, such as ______ → ______ → produces ______ → ______ activates ______ → ______ channels → ______ flow into the cell → ______ force of heart muscle

Dobutamine and DA, positive inotropic, vasodilation, dobutamine, cardiac, increased Ca, myocardial, contraction, IV infusion, short, decompensated HF, Dobutamine and DA, activates AC, cAMP, cAMP, protein kinase, phosphorylates Ca, increased Ca, Increased contraction

______

• Milrinone → increased intracellular cAMP concentration → increased intracellular Ca → Increased cardiac contractility

• Milrinone is usually given by IV infusion for short-term treatment of acute decompensated HF with low CO

• Milrinone reduces pulmonary vasculature resistance → utilized for acute treatment of pulmonary HTN and right HF

• Phosphodiesterase inhibitors prevent hydrolysis of cAMP → prolong protein kinase actions

Inotropic Drugs - Phosphodiesterase Inhibitors (PDE5-Is)

Inotropic Drugs - Phosphodiesterase Inhibitors (PDE5-Is)

• Milrinone → ______ concentration → ______ → ______

• Milrinone is usually given by ______ for ______-term treatment of acute ______ with ______

• Milrinone reduces ______ vasculature ______ → utilized for acute treatment of ______ and ______

• PDE5-Is prevent ______ → ______ actions

increased intracellular cAMP, increased intracellular Ca, Increased contractility, IV, short, decompensated HF, low CO, pulmonary, resistance, pulmonary HTN, right HF, cAMP hydrolysis, prolongs protein kinase